This is one of those wow deals
that science sometimes throws us.
Combining the effects of ultrasound and light is used to produce an
holographic image of any target area inside tissue. However we read these results, the promise is
huge. It is possible to produce a holographic
image of any part of one’s body with this.
The tools still need to be designed properly but this is a revolution in
imaging.
I do not know what the
theoretical limit of resolution will turn out to be but it is certainly way
better than present practice.
Again practical devices will
surely come quickly as there is nothing in terms of technology here that gas to
be overcome. So soon enough medicine
will be able to image a problem to a high level of accuracy and likely even act
on it directly using a range of linked devices.
You may not have noticed, but
medicine is swiftly converging on a complete reliance on remote surgical tools
for internal work. This will accelerate
it nicely.
A guide star lets scientists see deep into human tissue
February 11, 2011
A WUSTL scientist has invented the biomedical equivalent of the
astronomers' guide star.To correct for atmospheric blurring, astronomers
sometimes shine a laser into the sky near the spot where a telescope is
pointing. The laser beam energizes sodium atoms naturally present above the
stratosphere, producing a glowing artificial star called a guide star. The
astronomers use the ‘twinkling’ of this guide star to continuously compensate
for the effects of atmospheric turbulence on the light they are collecting from
nearby stars. The guide star thus allows astronomers to obtain much sharper,
more detailed images free of atmospheric blurring. Shown here is a laser beam
projected into the night sky from the Keck-2 telescope on Mauna Kea , Hawaii .
Credit: Paul Hirst/Creative Commons
Astronomers have a neat trick they sometimes use to compensate for the
turbulence of the atmosphere that blurs images made by ground-based telescopes.
They create an artificial star called a guide star and use its twinkling to
compensate for the atmospheric turbulence.
Lihong Wang, PhD, the Gene K. Beare Distinguished Professor of
Biomedical Engineering at Washington University in St. Louis, has invented a
guide star for biomedical rather than celestial imaging, a breakthrough that
promises game-changing improvements in biomedical imaging and light therapy.
Wang's guide star is an ultrasound beam that "tags" light
that passes through it. When it emerges from the tissue, the tagged light,
together with a reference beam, creates a hologram.
When a "reading beam" is then shown back through the
hologram, it acts as a time-reversal mirror, creating light waves that
follow their own paths backward through the tissue, coming to a focus at their
virtual source, the spot where the ultrasound is focused.
The technique, called time-reversed ultrasonically encoded (TRUE)
optical focusing, thus allows the scientist to focus light to a controllable
position within tissue.
Wang thinks TRUE will lead to more effective light imaging, sensing,
manipulation and therapy, all of which could be a boon medical research,
diagnostics, and therapeutics.
In photothermal therapy, for example, scientists have had trouble
delivering enough photons to a tumor to heat and kill the cells. So they either
have to treat the tumor for a long time or use very strong light to get enough
photons to the site, Wang says. But TRUE will allow them to focus light right
on the tumor, ideally without
losing a single tagged photon to scattering.
In both cases photons take random paths through tissue. Some are lost
(blue) but others (green) will reach the mirror on the other side of the
tissue. The mirror is a special phase conjugate mirror that turns the light
around and sends it back on its original path, as though time had been
reversed. Clever as this is, by itself it isn't very useful because the light
scatters again as is backtracks (left). In the new method, called TRUE,
ultrasound is focused into the tissue (small black ring). Light passing through
the ultrasound field is tagged by it and selectively returned by the mirror to
its virtual source, the ultrasound focus (right). Instead of scattering, the
light is brought to a focus inside the tissue. Credit: Lihong Wang
"Focusing light into a scattering medium such as tissue has
been a dream for years and years, since the beginning of biomedical
optics," Wang says. "We couldn't focus beyond say a millimeter, the
width of a hair, and now you can focus wherever you wish without any invasive
measure."
The new method was published in Nature Photonics, which appeared
online Jan. 16, and has since been spotlighted by Physics Today (both online
and in print) and in a Nature Photonics Backstage Interview.
The problem
Light is in many ways the ideal form of electromagnetic radiation for
imaging and treating biological tissues, but it suffers from an overwhelming
drawback. Light photons ricochets off nonuniformities in tissue like a steel
ball ricochets off the bumpers of an old-fashioned pinball machine.
This scattering prevents you from seeing even a short distance through
tissue; you can't, for example, see the bones in your hand. Light of the right
color can penetrate several centimeters into biological tissue, but even with
the best current technology, it isn't possible to produce high-resolution
images of objects more than a millimeter below the skin with light alone.
Ultrasound's advantages and drawbacks are in many ways complementary to
those of light. Ultrasound scattering is a thousand times weaker than optical
scattering.
Ultrasound reveals a tissue's density and compressibility, which are
often not very revealing. For example, the density of early-stage tumors
doesn't differ that much from that of healthy tissue.
Ultrasound tagging
The TRUE technique overcomes these problems by combining for the first
time two tricks of biomedical imaging science: ultrasound tagging and time
reversal.
Wang had experimented with ultrasound tagging of light in 1994 when he
was working at the M.D. Anderson Cancer Center in Houston, Texas . In experiments using a tissue phantom
(a model that mimics the opacity of tissue), he focused ultrasound into the
phantom from above, and then probed the phantom with a laser beam from the
side.
The laser light had only one frequency as it
entered the tissue sample, but the ultrasound, which is a pressure wave,
changed the tissue's density and the positions of its scattering centers. Light
passing through the precise point where the ultrasound was focused acquired
different frequency components, a change that "tagged" these photons
for further manipulation.
###
A conventional mirror (bottom) does not correct the distortion of a
wavefront produced by the water-filled bottle in this illustration. A time
reversal, or phase conjugating, mirror (top), on the other hand, produces a
wavefront that precisely retraces the path of the light, as if time were going
backward. It reverses the distortions introduced by the water, producing a
perfect image of the tiger. Credit: Wikimedia Commons
By tuning a detector to these frequencies, it is possible to sort
photons arriving from one spot (the ultrasound focus) within the tissue and to
discard others that have bypassed the ultrasonic beam and carry no information
about that spot. The tagged photons can then be used to paint an image of the
tissue at the ultrasound focus.
Ultrasound modulation of light allowed Wang to make clearer images of
objects in tissue phantoms than could be made with light alone. But this
technology selects only photons that have traversed the ultrasound field and
cannot focus light.
Time reversal
While Wang was working on ultrasound modulation of optical light, a lab
at the Langevin Institute in Paris
led by Mathias Fink, was working on time reversal of sound waves.
No law of physics is violated if waves run backward instead of forward.
So for every burst of sound (or light) that diverges from a source, there is in
theory a set of waves that could precisely retrace the path of the sound back
to the source.
To make this happen, however, you need a time-reversal mirror, a device
to send the waves backward along exactly the same path by which they arrived.
In Fink's experiments, the mirror consisted of a line of transducers that
detected arriving sound and fed the signal to a computer.
Each transducer then played back its sound in reverse — in synchrony
with the other transducers. This created what is called the conjugate of the
original wave, a copy of the wave that traveled backward rather than forward
and refocused on the original point source.
The idea of time reversal is so remote from everyday experience it is
difficult to grasp, but as Scientific American reported at the time, if you
stood in front of Fink's time-reversal "mirror" and said
"hello," you would hear "olleh," and even more bizarrely,
the sound of the "olleh," instead of spreading throughout the room
from the loudspeakers, would converge onto your mouth.
In a 1994 experiment, Fink and his colleagues sent sound through a set
of 2000 steel rods immersed in a tank of water. The sound scattered along all
the possible paths through the rods, arriving at the transducer array as a
chaotic wave. These signals were time-reversed and sent back through the forest
of rods, refocusing to a point at the source location.
In effect, time reversal is a way to undo scattering.
Combining the tricks
Wang was aware of the work with time reversal, but at first couldn't
see how it might help solve his problem with tissue scattering.
In 2004, Michael Feld, a physicist interested in biomedical imaging,
invited Wang to give a seminar at the Massachusetts Institute of Technology.
"At dinner we talked about time reversal," Wang says. "Feld was
thinking about time reversal, I was thinking about time reversal, and so was
another colleague dining with us."
"The trouble was, we couldn't figure out how to use it. You know,
if you send light through a piece of tissue, the light will scatter all over
the place, and if you capture it and reverse it, sending it back, it will still
be scattered all over the place, so it won't concentrate photons."
"And then 13 years after the initial ultrasound-tagging
experiments, I suddenly realized I could combine these two techniques.
"If you added ultrasound, then you could focus light into tissue
instead of through tissue. Ultrasound tagging lets you reverse and send back
only those photons you know are going to converge to a focus in the
tissue."
"Ultrasound provides a virtual guide star, and to make optical
time reversal effective you need a guide star," Wang says.
A time-reversal mirror for light
It's much easier to make a time-reversal mirror for ultrasound than for
light. Because sound travels slowly, it is easy to record the entire time
course of a sound signal and then broadcast that signal in reverse order.
But a light wave arrives so fast it isn't possible to record a time
course with sufficient time resolution. No detector will respond fast enough.
The solution is to record an interference pattern instead of a time course.
The beam that has gone through the tissue and a reference beam form an
interference pattern, which is recorded as a hologram by a special
photorefractive crystal.
Then the wavefront is reconstructed by sending a reading beam through
the crystal from the direction opposite to that of the reference beam. The
reading beam reconstitutes a reversed copy of the original wavefront, one that
comes to a focus at the ultrasound focus.
Unlike the usual hologram, the TRUE hologram is dynamic and constantly
changing. Thus it is able to compensate for natural motions, such as breathing
and the flow of blood, and it adapts instantly when the experimenter moves the
ultrasonic focus to a new spot.
More photons to work with
Wang expects the TRUE technique for focusing light within tissue will
have many applications, including optical imaging, sensing, manipulation and
therapy. He also mentions its likely impact on the emerging field of
optogenetics.
In optogenetics, light is used to probe and control living neurons that
are expressing light-activatable molecules or structures. Optogenetics may
allow the neural circuits of living animals to be probed at the high speeds
needed to understand brain information processing.
But until now, optogenetics has suffered from the same limitation that
plagues optical methods for studying biological tissues. Areas of the brain
near the surface can be stimulated with light sources directly mounted on the
skull, but to study deeper areas, optical fibers must be inserted into the
brain.
TRUE will allow light to be focused on these deeper areas without
invasive procedures, finally achieving the goal of making tissue transparent at
optical frequencies.
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